Biology Reference
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¯uorometric assay, which uses di¨erent esters ( BATDA) and a chelator ( Eu 3 )
(Blomberg et al., 1996). Measurement of quanti®able, released intracellular
protein has also been described as a method of measuring CTL killing ( Kyburz
et al., 1993).
CTL in Primary HIV Infection
Primary HIV infection represents the period immediately post infection with
the HIV virus, which is characterized by a number of immune changes and
nonspeci®c clinical symptoms such as rash, fever, and lymphadenopathy, which,
for the most part, resolves spontaneously, leading to a long asymptomatic
period. The patient is characterized with lack of HIV antibodies and high
levels of plasma HIV-1 RNA that subsequently declines and reaches a quasi-
steady state after about 6 months (Musey et al., 1997b). Whereas antibody is
detectable at about 3±6 months following infection, HIV-speci®c CTL have
been found in early primary infection period corresponding with the time of
the initial decline in viremia ( Wilson et al., 2000). The emergence of vigorous,
HIV-speci®c CTL in most individuals has been implicated as a reason for the
declining viremia ( Price et al., 1999; Shankar et al., 1999).
In several cross-sectional and prospective patient studies, a wide range of
CTL responses have been reported. In one study, fresh PBMC from 23 patients
(followed for 2 years following primary infection) were tested for the presence
of HIV-speci®c CTL. Most (74%) of the donor PBMC contained HIV-speci®c
CTL at a range of 10±26% above control vaccinia (at 100:1 E:T ratio) using the
chromium release assay. HIV-1 env gene product was recognized by 94% of the
patients whereas 29% and 12% of the patients recognized HIV-1 Gag and Pol,
respectively. The same study also found that HIV-speci®c CTL were mostly
CD8 cells, although 22% of the patients also had CD4 CTL. These ®ndings
were found to be similar when the patients were studied at intervals of 3±6
months (Musey et al., 1997).
Memory T cells (as measured by limiting dilution assay, or LDA) are also
induced during this period and they reach their peak levels during primary
infection followed by subsequent decline. Most responses have equally been
targeted at the HIV-1 env gene products and, to a lesser extent, the HIV-1 gag
gene products. The precursor frequencies per million PBMC in one study were
found to range from 0 to 446 for Env, 0 to 333 for Gag, and 0 to 364 for Pol
gene products. With the advent of direct enumeration by tetramers, these are
thought to be low estimates by as much as two orders of magnitude (Mylin et
al., 2000). These frequencies were, however, found to be variable in the same
individual when followed over time. The HIV-1 Env-speci®c memory CTL re-
sponses where found to be inversely correlated with viral load and plasma level
of infectious virus, whereas the HIV-1 Gag-speci®c memory CTL responses
inversely correlated with plasma levels of infectious virus and not viral load.
This and similar studies indicate that the env gene product is the most dominant
gene product involved in the control of viral replication (Musey et al., 1997).
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